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Reply:

We agree with these authors that one of the main problems concerning patients infected with human immunodeficiency virus (HIV)who have hepatocellular carcinoma (HCC) is the high rate of dropouts on the waiting list for liver transplantation (LT).1 Although controversial results have been published regarding the prognosis of HCC in HIV-infected patients, the kinetics of tumor progression in HIV-infected subjects seems to be particularly rapid.2, 3 We need specific markers of poor prognosis and HCC tumor progression in these patients in order to improve patient selection and guide neoadjuvant and adjuvant therapies.

As for the CD4 cell count, we agree with the authors that great caution is necessary regarding the indications of LT in patients with a CD4 T cell count lower than 100/μL. However, because of the lack of clear data to demonstrate the influence of the CD4 T cell count on HCC progression before LT and on survival after LT, it is difficult to exclude such patients from a transplantation program. In the event of a low CD4 cell count before LT, one of the main objectives during the post-LT period is to prevent a marked drop in the CD4 cell count; for this reason, a rapid reintroduction of highly active antiretroviral therapy (HAART) after LT needs to be discussed in such cases.

We also agree with the authors that mTOR (mammalian target of rapamycin) inhibitor-based immunosuppressive regimens must be tried in such patients.4 We contributed to the Silver study on sirolimus after LT for HCC, and rapamycin and sirolimus are currently being evaluated in our center for the treatment of HIV-infected patients who have undergone transplantation for HCC. However, mTOR inhibitors are metabolized by cytochrome P4503A4, and interactions with HAART therapy need to be avoided. Moreover, Raltegravir, an HIV-1 integrase inhibitor that is metabolized primarily by UGT1A1 (uridine diphosphate glucuronosyltransferase 1 family, polypeptide A1) and is not affected by cytochrome P450 inhibitors or inducers, could be suggested as the drug of choice among nucleoside reverse transcriptase inhibitors.5

In conclusion, the definition of new prognostic markers for HCC before LT, an active neoadjuvant therapy that can prevent dropouts, and the specific management of immunosuppression are the main objectives to be achieved in the very near future with respect to these HIV-infected patients.

References

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  • 1
    Vibert E, Duclos-Vallée JC, Ghigng MR, Hoti E, Salloum C, Gaettier C, et al. Liver transplantation for hepatocellular carcinoma: The impact of human immunodeficiency virus infection. Hepatology 2011; 53: 475-482.
  • 2
    Puoti M, Bruno R, Soriano V, Donato F, Gaeta GB, Quinzan GP, et al. Hepatocellular carcinoma in HIV-infected patients: epidemiological features, clinical presentation and outcome. AIDS 2004; 18: 2285-2293.
  • 3
    Brau N, Fox RK, Xiao P, Marks K, Naqvi Z, Taylor LE, et al. Presentation and outcome of hepatocellular carcinoma in HIV-infected patients: a U.S. Canadian multicenter study. J Hepatol 2007; 47: 527-537.
  • 4
    Di Benedetto F, Di Sandro S, De Ruvo N, Montalti R, Ballarin R, Guerrini GP, et al. First report on a series of HIV patients undergoing rapamycin monotherapy after liver transplantation. Transplantation 2011; 89: 733-738.
  • 5
    Bickel M, Anadol E, Vogel M, Hofmann WP, von Hentig N, Kuetscher J, et al. Daily dosing of tacrolimus in patients treated with HIV-1 therapy containing a ritonavir-boosted protease inhibitor or raltegravir. J Antimicrob Chemother 2011; 65: 999-1004.

Jean-Charles Duclos-Vallée M.D.* † ‡, René Adam M.D., Ph.D.* § ¶, Eric Vibert M.D.* † ‡, Didier Samuel M.D.* † ‡, * Assistance Publique–Hôpitaux de Paris, Hôpital Paul Brousse, Centre Hepato-Biliaire, Villejuif, France, † Institut National de la Santé et de Recherche Médicale (INSERM), Unité 785, Villejuif, France, ‡ Université Paris-Sud, Unité Mixte de Recherche (UMR)-S785, Villejuif, France, § INSERM, Unité 776, Villejuif, France, ¶ Université Paris-Sud, UMR-S776, Villejuif, France.